The Old World monkeys and apes are natural hosts for many infectious agents (viruses and microbes) that can cause human disease. These include such pathogens as the HIV/SIV lentiviruses, Ebola viruses, herpesviruses, and numerous other exogenous and endogenous viruses. Understanding the origins and transmission patterns of such agents requires first knowing the phylogeny of the host species. Within recent years, the molecular phylogeny of the great apes and humans has finally been resolved, with statistical confidence, by analysis of their entire mitochondrial DNA (mtDNA) genomes and several unlinked loci encoded by nuclear DNA (nDNA). Following this successful strategy, here we propose to produce and analyze the DNA sequence data necessary for inference of a statistically-robust molecular phylogeny of the major lineages of Old World monkeys. The Old World monkeys are divided into two subfamilies, the colobines (Asian langurs and leaf-monkeys, and African colobus monkeys; over 30 species in about 9 genera) and the cercopithecines (macaques, baboons, mangabeys, guenons, and green monkeys; over 50 species in about 10 genera). We plan to resolve the phylogeny of these genera, which are carriers of many agents that cause human disease, by doing the following: SPECIFIC AIM 1: We will purify, clone, and sequence the entire mtDNA genomes from 9 cercopithecines (patas, talapoin, swamp monkey, a guenon, green monkey, mandrill, a macaque, and two mangabeys), 9 colobines (the African olive, red, and guereza colobus monkeys, and the Asian Hanuman, dusky and douc langurs, and a leaf, golden, and proboscis monkey), and two New World monkeys (squirrel and howler monkey) as additional outgroups. SPECIFIC AIM 2: Using the same species as above, we will sequence several unlinked nDNA loci, totaling about 15 to 20 kilobases per species. SPECIFIC AIM 3: These mtDNA and nDNA sequences will be analyzed phylogenetically and statistically to test key hypotheses concerning monkey phylogeny, as well as to generate and test new hypotheses. Taken together, these genetic data should produce a robust phylogeny, showing both the branching order and the times of divergence of the major lineages of OWMs. This phylogeny will provide the proper evolutionary framework for inferences about biological processes such as the origin of infectious agents, the coevolution of hosts and pathogens, adaptation of host and pathogen molecules, and patterns of disease transmission within and between species.